A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Lucitanib
- Conditions
- Breast Cancer
- Sponsor
- Clovis Oncology, Inc.
- Enrollment
- 178
- Locations
- 33
- Primary Endpoint
- Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with FGF aberrant metastatic breast cancer, as well as in the treatment of patients with biomarker negative (FGF non-aberrant) metastatic breast cancer.
Detailed Description
Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3, VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models. The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in patients not known to have FGF abnormalities. Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in breast cancer patients with and without alterations of the FGF pathway.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed metastatic breast cancer relapsed or refractory to approved standard available treatment
- •Prior treatment with standard first line therapy in the metastatic setting
- •Availability of tumor tissue sufficient for confirmatory testing of FGFR1 and 11q amplification status
- •Demonstrated progression of disease by radiological or clinical assessment (Measurable disease according to RECIST Version 1.1 is NOT required for enrollment)
- •Estimated life expectancy \>6 months
Exclusion Criteria
- •Current or recent treatment with biologic anticancer therapies
- •Ongoing AEs from prior anticancer therapies
- •Active central nervous system (CNS) metastases
- •Clinically significant or uncontrolled hypertension or cardiac disease
- •Females who are pregnant or breastfeeding
Arms & Interventions
Cohort A: Lucitanib (CO-3810) 10 mg daily
10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
Intervention: Lucitanib
Cohort B: Lucitanib (CO-3810) 15 mg daily
15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.
Intervention: Lucitanib
Cohort C: Lucitanib (CO-3810) 10 mg daily
10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.
Intervention: Lucitanib
Outcomes
Primary Outcomes
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
Time Frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Secondary Outcomes
- Duration of Response (DR) by RECIST v1.1(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months)
- Objective Response Rate (ORR) by RECIST v1.1(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months)
- Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score(From Cycle 1 Day 1 until end of treatment, assessed up to 29 months)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax(Study Day -7 to Study Day 1, or approximately 8 days)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax(Study Day -7 to Study Day 1, or approximately 8 days)
- Disease Control Rate (DCR) by RECIST v1.1(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months)
- Overall Survival(Cycle 1 Day 1 to date of death, assessed up to 29 months)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast(Study Day -7 to Study Day 1, or approximately 8 days)
- Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf(Study Day -7 to Study Day 1, or approximately 8 days)
- Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf(Study Day -7 to Study Day 1, or approximately 8 days)